Leydig cells isolated from rat testis and thyrotropic and gonadotropic cells from rat pituitaries are studied in vitro to compare their physiology in old and young rats and in normal vs. uremic rats. Testosterone production, cell number of gonadotrophin receptors, and cAMP production are assayed in order to investigate the alterations of Leydig cell function in aging and uremia. Production of TSH in response to TRH, production of LH and FSH and their subunits in response to LRH and receptors for TSH and LRH will be measured in an attempt to elucidate altered function of pituitary secretory cells with age and in uremia. Hypothalamic content of LRH, dopamine, catecholamines and alpha and beta adrenergic and dopaminergic receptors will also be determined. Work to date indicates that the Leydig cell defect is reversible by in vivo treatment of aged rats with gonadotropin and that it is not mediated by loss of receptors, cyclase, or any single enzyme in the steroidogenic cascade. Deficient function of aged pituitary cells in vitro has been confirmed and a workable assay for LRH has been initiated in our laboratory.